Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma
| Autor: | Arpa Surapaitoon, Chawalit Pairojkul, Narong Khuntikeo, Jeffrey M. Bethony, Eimorn Mairiang, Sutas Suttiprapa, Paul J. Brindley, Banchob Sripa |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment Peripheral blood mononuclear cell Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Fibrosis parasitic diseases medicine Opisthorchis viverrini Allele biology business.industry General surgery fungi Hepatobiliary disease medicine.disease biology.organism_classification 3. Good health 030104 developmental biology Infectious Diseases Cytokine Opisthorchis Viverrini Infection 030220 oncology & carcinogenesis Immunology Parasitology business |
| Zdroj: | The Korean Journal of Parasitology. 55:295-304 |
| ISSN: | 1738-0006 0023-4001 |
| DOI: | 10.3347/kjp.2017.55.3.295 |
| Popis: | Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1β, IL-6, IFN-γ, LT-α, and TNF-α were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-1β-511C/T, IL-6-174G/C, IFN-γ +874T/A, LT-α +252A/G, and TNF-α -308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-α +252A/G and TNF-α -308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-γ +874T/A were significantly higher than the variants in CCA cases. IFN-γ +874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6 -174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA. |
| Databáze: | OpenAIRE |
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